Project Summary This 2-site (Florida International University, Yale University) R01 project proposes to confirm attention bias modification treatment (ABMT) as an efficacious treatment for social anxiety disorder (SAD) in peripubertal youth ages 10 to 14 years, and examine the mechanisms of ABMT's clinical efficacy. SAD is prevalent, chronic, and impairing. Response rates to evidence-based treatments (EBTs) are markedly lower for SAD than other anxiety disorders, and limited insights exist about mechanisms of positive outcome for those youths who do respond to existing EBTs. Alternative treatment options are therefore critically needed, particularly for translational neuroscience approaches that arise from NIMH's experimental therapeutics approach. ABMT is such an approach, as it is grounded in cognitive neuroscience theory and methods to address perturbed attention that operates on extremely rapid time scales. In accordance with NIMH's experimental therapeutics approach, we collected data in our preliminary work that support ABMT's feasibility and acceptability, and identifies a putative target mechanism. We next collected data demonstrating an effect on the target (i.e., target engagement) and linking changes in the target to clinical improvements (i.e., target validation). Specifically, we collected data on targeted rapidly deployed processes in event related potentials (ERP), and found that youth with SAD show enhanced P1 amplitudes for socially threatening stimuli compared with typically developing controls, thereby indicating enhanced neural processing during attention orienting to social threat, providing a putative ABMT target. Our data further show ABMT to reduce both anxiety severity (i.e., signal of clinical efficacy) and P1 amplitudes, with these clinical and neural changes occurring together. These data position us to propose a confirmatory efficacy R01 to (1) re-demonstrate target engagement, (2) re-demonstrate the effects of ABMT on social anxiety symptom severity, (3) demonstrate target validation, and (4) evaluate the maintenance of outcomes. We also will (5) explore attention control as a moderator of outcomes. We will randomize 260 (N = 130 at each site) clinic referred youths ages 10-14 years who meet for SAD to either ABMT or a Neutral Control Task (NCT). We hypothesize that attention orienting to social threat, measured using P1 ERP amplitudes in the dot-probe task, and social anxiety symptom severity will be significantly lower at post-treatment and 6-month Follow-Up in the ABMT arm compared with the NCT arm. We further hypothesize that P1 amplitudes will mediate reductions in social anxiety symptom severity. This project will provide a rigorous, sufficiently powered mechanistic test of ABMT for SAD in youth. Supportive findings would position us to pursue an effectiveness trial of ABMT in community and practice settings. Findings will also provide insight on attention control's promise for future research relating to precision medicine approaches.